Efficient Asymmetric Synthesis of 2,6-Disubstituted 2H-Dihydropyrans via a Catalytic Hetero-Diels-Alder/Allylboration Sequence

Article abstract of DOI:10.1002/adsc.200303127

[4 + 2] Cycloaddition of (E)-3-borylacrolein 1 with ethyl vinyl ether, catalysed by chromium complex (1R,25) or (15,2R) 2, led to the corresponding cycloadducts with high diastereo- and enantioselectivities. Further reaction with aldehydes offers an attractive asymmetric route to synthetically useful substituted 3,4-dihydro-2H-pyrans.

Full text of DOI:10.1002/adsc.200303127

COMMUNICATIONS
Efficient Asymmetric Synthesis of 2,6-Disubstituted 2H-
Dihydropyrans via a Catalytic Hetero-Diels Alder/Allylboration
Sequence
Michael Deligny, FranÁois Carreaux,* LoÔc Toupet, Bertrand Carboni
¡
¡
¬
Synthese et Electrosynthese Organique, UMR CNRS 6510, Bat 10A, Institut de Chimie, and GMCM, CNRS, Universite de
Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
Fax: ( ‡ 33)-2-23-23-57-34, e-mail: francois.carreaux@univ-rennes1.fr
Received: July 31, 2003; Accepted: September 2, 2003
Abstract: [4 ‡ 2] Cycloaddition of (E)-3-borylacro-
lein 1 with ethyl vinyl ether, catalysed by chromium
complex (1R,2S) or (1S,2R) 2, led to the correspond-
ing cycloadducts with high diastereo- and enantio-
selectivities. Further reaction with aldehydes offers
an attractive asymmetric route to synthetically
useful substituted 3,4-dihydro-2H-pyrans.
Scheme 1.
Keywords: allylboration; asymmetric catalysis; bor-
onic esters; chromium complex; dihydropyrans; het-
ero-Diels Alder
potential of this strategy for further applications in
natural products synthesis.
Hetero-Diels Alder reactions provide a powerful meth- Results and Discussion
od for the synthesis of oxygen-containing six-membered
heterocycles, an important substructure in a large We first examined the [4 ‡ 2] cycloaddition of the
variety of bioactive compounds. This explains the wide heterodiene 1 to ethyl vinyl ether in the presence of
range of substrates and catalysts hitherto involved in 5 mol % of catalyst 2, according to Jacobsen×s proce-
theses cycloadditions.[1] On the other hand, due to their dure.[10] This reaction was carried out with 4 ä molecular
great versatility, organoboranes have emerged as espe- sieves as desiccant and the dienophile as solvent and
cially attractive building blocks in organic synthesis.[2,3] afforded the expected dihydropyran 3 in good yield
Thus, the replacement of the carbon-boron bond by a (85%) with high diastereo- and enantiomeric excess ( >
new carbon-carbon or carbon-heteroatom bond has 95% de and 96% ee). The stereoselectivities were
1
been largely employed in stereocontrolled syntheses of measured on the cycloadduct by H NMR and GC
diversely substituted alkenes, the Suzuki Miyaura cou- analysis using a chiral stationary phase, as well as by
pling reaction being probably the most attractive comparison with a racemic mixture previously prepared
process.[4] Cycloadditions involving an alkenyl- or dienyl in the presence of Yb(fod)3 as catalyst.[9] It is worthy of
boronic esters have been also reported, but rarely in note that the presence of the boronic ester group
asymmetric versions.[5 7] In all cases, stoichiometric significantly increased the rate of the reaction: 100%
amounts of chiral auxiliaries at the borylated moiety conversion after 2 h at rt, instead of 24 48 h for the
or at a proximal position have been employed. We have same substrate with a methyl or an aryl substituent.[10]
recently described a new approach for the synthesis of Other vinyl ethers engaged in such cycloadditions with 1
racemic dihydropyrans derivatives, based on a multi- gave unsatisfactory results.
component reaction: an inverse electron-demand het-
In order to establish the stereochemistry of 3,
ero-Diels Alder reaction of 3-borylacrolein 1, followed oxidation of the cycloadduct by H2O2/NaOH or AcONa
by an allylboration (Scheme 1).[8,9] Recent impressive or by triethylamine N-oxide was first tried. This trans-
results obtained by Jacobsen et al. in the field of formation, which was proven to proceed with retention
asymmetric catalysis with chiral chromium(III) com- of configuration, was found to give modest yields of the
plexes[10] led us to study the asymmetric version of our corresponding allylic alcohol and to be unreproducible;
sequence,[11] which would undoubtedly increase the this led us to reduce first the double bond of the
Adv. Synth. Catal. 2003, 345, 1215 1219
DOI:10.1002/adsc.200303127
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1215

Michael Deligny et al.
COMMUNICATIONS
Scheme 2.
Scheme 3.
Scheme 4.
cyclohexene ring before achieving the oxidation the allylboration process was confirmed by performing
(Scheme 3). The secondary alcohol 4 was obtained in a the same reaction with the enantiomer (2R,4R)-3.
95% yield. Analysis of the Mosher×s ester confirmed the Within the experimental errors, the same purity was
isomeric purity of 3 previously measured by chiral gas measured in both cases, closely paralleling the enantio-
chromatography and allowed us to determine the meric excess of the starting material. The relative
1
absolute configurations by H NMR: (2S,4R)-4 and configuration of the stereogenic centres is in full agree-
therefore (2S,4S)-3.[12] Similar experiments performed ment with a cyclic chair-like transition state A with the
with the (1R,2S)-enantiomer of 2 gave the same results phenyl group of benzaldehyde in an equatorial position,
in terms of yield and stereoselectivities. No attempt was that was currently observed with other cyclic allylbor-
made in this preliminary work to decrease the amount of onic esters.[7d,13] The results obtained with other repre-
catalyst and to correlate it with the efficiency of the sentative aldehydes are collected in Table 1. In all cases,
cycloaddition.
dihydropyrans 5a g were obtained in good yields and
Having in hand an efficient asymmetric synthesis of 3, high stereochemical purities. An X-ray crystal structure
we next turned our attention to its reactivity towards determination of 5g established the absolute configu-
aldehydes (Scheme 4). Reaction of the cyclic allylbor- rations of its four stereocentres. (Fig. 1).[14] Unfortu-
ane (2S,4S)-3 with benzaldehyde in toluene for 12 h at nately, attempts to carry out the two steps, cycloaddi-
708C gave after hydrolysis the corresponding homo- tion/allylboration, in the same pot, gave unsatisfactory
allylic alcohol 5a in 85% yield. A > 95% diastereoiso- results (low yield and ee).[15]
1
meric excess was determined by H NMR, while the
In summary, we have developed an asymmetric
enantiomeric purity (95% ee) was measured by chiral version of the hetero-Diels Alder cycloaddition of
gas chromatography. Moreover, the stereospecificity of (E)-3-borylacrolein to ethyl vinyl ether catalysed by a
1216
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Adv. Synth. Catal. 2003, 345, 1215 1219

Synthesis of 2,6-Disubstituted 2H-Dihydropyrans
COMMUNICATIONS
Table 1. Allylation reactions of (2S,4S)-3 using various aldehydes.
Product
R[a]
Yield [%][a]
ee [%][b]
Absolute conf.
5a
5b
5c
5d
5e
5f
Ph
85
84
77
80
82
87
78
95[c]
96
93
(2S,6R,7R)
(2S,6R,7R)
(2S,6R,7R)
(2S,6R,7R)
(2S,6R,7R)
(2S,6R,7R)
(2S,6R,7S,8R)
4-MeO-C6H4
4-Cl-C6H4
4-F-C6H4
PhCH2
PhCH2CH2
(2R)-Ph-CH(OTBDPS)
96
96
96
c
5g
95
[a]
Yields of isolated products after column chromatography.
Determined by chiral GC analysis.
The same reaction performed with (2R,4R)-3 gave the opposite enantiomer with the same ee.
[b]
[c]
values downfield from tetramethylsilane. High resolution mass
spectra were obtained on an MS/MS ZABSpec TOF Micro-
¬
mass at the Centre Regional de Mesures Physiques de l×Ouest.
Optical rotations were recorded using a Perkin Elmer Model
341 polarimeter. Analytical thin layer chromatography was
performed on Merck Silica gel 60 F254 aluminium. Column
chromatography was performed on Merck silica gel (Geduran
0.063 0.200 mm). Enantiomeric excesses were determined by
gas chromatography performed using a Varian CP3380 GC
unit equipped with a capillary chiral column Varian WCOT
Fused Silica 25 m  0.25 mm coated CP Chirasil-dex CB DF ˆ
0.25. Chromatography conditions: carrier gas argon; injection
temperature 2008C; detector temperature 2508C.
(2S)-Ethoxy-(4S)-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)-3,4-dihydro-2H-pyran (3):
182 mg (1 mmol) of 3-borylacrolein 1, 150 mg of 4 ä molecular
sieves, 24 mg (0.05 mmol, 5 mol %) of dimer (1S,2R)-catalyst 2
in 960 mL of ethyl vinyl ether were placed in an oven-dried 10-
mL round-bottom flask. After stirring for 2 hours at rt, the
reaction mixture was diluted with pentane and filtered through
a pad of celite. The solvents were removed under vacuum and
the product distilled with a K¸gelrohr apparatus (oven: 908C, 1
mmHg) to afford 3 as a clear oil; yield: 215 mg (0.085 mmol,
Figure 1. X-ray crystal structure of 5g.
chiral (Schiff base)chromium(III) complex. Further
reactions with aldehydes allow access to a series of 2,6-
disubstituted dihydropyrans with a high diastereo- and
enantiomeric purity. Studies to expand the scope of this
three-components reaction and to apply this strategy in
asymmetric synthesis of natural products, particularly in
the field of carbohydrate chemistry, are ongoing.
1
85%). H NMR (CDCl3): d ˆ 1.26 (t, 3H, J ˆ 7.1 Hz), 1.30 (s,
12H), 1.81 (m, 1H), 2.19 (m, 2H), 3.64 (dq, 1H, J ˆ 9.9, 7.1 Hz),
3.90 (dq, 1H, J ˆ 9.9, 7.1 Hz), 4.88 (dd, 1H, J ˆ 6.1, 4.5 Hz), 5.04
(dd, 1H, J ˆ 3.5, 3.1 Hz), 6.29 (dd, 1H, H-5, J ˆ 6.2, 2.0 Hz);
13C NMR (CDCl3): d ˆ 15.7 (CH3), 25.0 (CH3), 25.3 (CH3), 29.1
(CH2), 63.8 (CH2), 83.7 (C), 97.1 (CH), 103.1 (CH), 139.4 (CH);
‡
HRMS (EI): [M .OC2H5] calcd. for C11H18O3B: 209.1349;
found: 209.133; [a]D25: ‡ 27.3 (c 1.41, CH2Cl2). Assay of
enantiomeric excess: Chiral GC analysis (Chirasil-dex; 80
to 1008C at 58C/min, then 100 to 1808C at 0.58C/min, 15 psi
head column pressure; tR(major) ˆ 63.14 min, tR(minor) ˆ
64.28 min).
Experimental Section
All chemicals were used as received unless otherwise noted.
Catalyst (1S,2R)-2 was prepared according to the literature [10]
,
while its enantiomer was kindly donated by Eric N. Jacobsen
and D. Chavez. Toluene and ethyl vinyl ether were distilled
from sodium/benzophenone. All aldehydes were freshly dis-
tilled prior to use. (2R)-Phenyl[(trimethylsilyl)oxy]acetalde-
hyde[16] and 3-borylacrolein 1[8] were prepared according to
literature procedures. 8 12 Mesh 4 ä molecular sieves were
dried in a vacuum oven for 12 hours at 1608C. NMR spectra
were recorded with a Br¸ker spectrometer at 300 (1H NMR)
and 75 (13C NMR) MHz. Chemical shifts are reported as d
(2S)-Ethoxy-(4R)-hydroxy-3,4-dihydro-2H-pyran (4)
In an oven-dried 10-mL round-bottom flask, 430 mg
(1.67 mmol) of (2S,4S)-(3), 170 mg of Pd/C 10% in 10 mL of
ethyl acetate were stirred for one hour under hydrogen
atmosphere. After filtration through celite and evaporation
Adv. Synth. Catal. 2003, 345, 1215 1219
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Michael Deligny et al.
COMMUNICATIONS
of solvent, the residue was taken up in 10 mL of THF. At 08C,
676 mL (6.76 mmol) of H2O2 35% w/w in water and 2.2 mL
(6.76 mmol) of 3 M NaOH were successively added. After
stirring for one hour at 08C, the mixture was saturated with
solid K2CO3 and stirred for 30 min. The mixture was extracted
with ether and dried over anhydrous MgSO4, filtered and
concentrated under vacuum. The crude product was purified
by column chromatography (heptane/AcOEt, 1/1) on SiO2
deactivated with triethylamine to afford 4; yield: 222 mg
(1.59 mmol, 95%). 1H NMR (CDCl3): d ˆ 1.28 (t, 3H, J ˆ
7.1 Hz), 1.94 (m, 4H), 3.54 (m, 3H), 3.83 (dq, 1H, J ˆ 9.7,
7.1 Hz), 4.07 (m, 2H), 4.81 (t, 1H, J ˆ 3.1 Hz); 13C NMR
(CDCl3): d ˆ 15.5 (CH3), 33.2 (CH2), 37.1 (CH2), 56.2 (CH2),
64.2 (CH2), 64.6 (CH), 98.3 (CH); [a]D25: ‡ 43.1 (c 1.00, CHCl3).
(CH), 128.5 (CH), 128.6 (CH), 133.7 (C), 138.6 (C). Anal calcd.
for C14H17ClO3: C 62.57, H 6.38; found: C 62.76, H 6.81. [a]D25:
‡ 48.4 (c 1.00, CHCl3). Assay of enantiomeric excess: Chiral
GC analysis (Chirasil-dex; 80 to 1008C at 58C/min, then 100 to
1808C at 18C/min, 10 psi head column pressure; tR(major) ˆ
86.62 min, tR(minor) ˆ 85.58 min).
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5d): yield: 80%
1
(202 mg, 0.80 mmol). H NMR (CDCl3): d ˆ 1.30 (t, 3H, J ˆ
7.1 Hz), 2.31 (m, 2H), 3.43 (br d, 1H, J ˆ 2.2 Hz), 3.67 (dq, 1H,
J ˆ 9.5, 7.1 Hz), 4.06 (dq, 1H, J ˆ 9.5, 7.1 Hz), 4.36 (m, 1H), 4.65
(dd, 1H, J ˆ 7.3, 2.2 Hz), 4.83 (t, 1H, J ˆ 5.4 Hz), 5.44 (m, 1H),
5.83 (m, 1H), 7.09 (m, 2H), 7.44 (m, 2H); 13C NMR (CDCl3):
d ˆ 15.2 (CH3), 31.0 (CH2), 64.6 (CH2), 76.2 (CH), 78.7 (CH),
98.5 (CH), 115.0 (CH), 115.4 (CH), 125.1 (CH), 125.4 (CH),
128.8 (CH), 129.0 (CH), 136.2 (C), 136.3 (C), 160.0 (C), 164.0
.
‡
À
(C); HRMS (EI): [M OCH2CH3] , calcd. for C12H12FO2:
207.0821; found: 207.083. Anal calcd. for C14H17FO3: C 68.16, H
7.63; found: C 68.16, H 7.81. [a]D25: ‡ 13.7 (c 1.00, CHCl3). Assay
of enantiomeric excess: Chiral GC analysis (Chirasil-dex; 80 to
1008C at 58C/min, then 100 to 1808C at 18C/min, 10 psi head
General Procedure for the Allylboration Reactions
A solution of 1 mmol of 3 and 2 mmol of aldehyde in 2 mL of
toluene was heated at 708C. The reaction was monitored by
GC and allowed to stir until complete consumption of 3. After
addition of a saturated solution of NH4Cl, the aqueous layer
was extracted twice with CH2Cl2. Combined organic layers
were washed with saturated NaCl, dried over anhydrous
MgSO4, filtered and concentrated under vacuum. The crude
product was purified by column chromatography (heptane/
AcOEt, 9/1) on SiO2 deactivated with triethylamine to yield
5a g as indicated in Table 1.
column
68.70 min).
pressure;
tR(major) ˆ 69.88 min,
tR(minor) ˆ
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5e): yield: 82%
1
(203 mg, 0.82 mmol). H NMR (CDCl3): d ˆ 1.25 (t, 3H, J ˆ
7.1 Hz), 2.30 (m, 2H), 2.60 (br d, 1H, J ˆ 6.6 Hz), 3.00 (m, 2H),
3.66 (dq, 1H, J ˆ 9.5, 7.1 Hz), 3.88 (m, 1H), 4.09 (dq, 1H, J ˆ 9.5,
7.1 Hz), 4.20 (m, 1H), 4.80 (t, 1H, J ˆ 5.4 Hz), 5.70 (m, 1H), 5.89
(m, 1H), 7.31 (m, 5H); 13C NMR (CDCl3): d ˆ 15.7 (CH3), 31.4
(CH2), 40.0 (CH2), 64.9 (CH2), 74.7 (CH), 75.7 (CH), 98.9
(CH), 125.4 (CH), 126.6 (CH), 126.9 (CH), 128.9 (CH), 129.8
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5a): yield: 85%
1
(198 mg, 0.85 mmol). H NMR (CDCl3): d ˆ 1.31 (t, 3H, J ˆ
]‡
À
(CH), 138.9 (C); HRMS (EI): [M HOC2H5 , calcd. for
7.1 Hz), 2.30 (m, 2H), 3.00 (br s, 1H), 3.62 (dq, 1H, J ˆ 9.6,
7.1 Hz), 4.05 (dq, 1H, J ˆ 9.6, 7.1 Hz), 4.39 (m, 1H), 4.61 (d, 1H,
J ˆ 7.5 Hz), 4.82 (t, 1H, J ˆ 5.4 Hz), 5.42 (m, 1H), 5.80 (m, 1H),
7.40 (m, 5H); 13C NMR (CDCl3): d ˆ 15.6 (CH3), 31.4 (CH2),
64.9 (CH2), 77.2 (CH), 79.1 (CH), 98.9 (CH), 125.3 (CH), 125.8
(CH), 127.7 (CH), 128.5 (CH), 128.8 (CH), 140.3 (C); HRMS
C13H14O2: 202.0994; found: 202.099. [a]D25: ‡ 23.7 (c 1.00,
CHCl3). Assay of enantiomeric excess: Chiral GC analysis
(Chirasil-dex; 80 to 1008C at 58C/min, then 100 to 1808C at
18C/min, 10 psi head column pressure; tR(major) ˆ 75.93 min,
tR(minor) ˆ 76.66 min).
.
‡
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5f): yield: 87%
À
À
(EI): [M CHOH Ph] , calcd. for C7H11O2: 127.0759; found:
127.076; [a]D25: ‡ 24.9 (c 1.03, CHCl3). Assay of enantiomeric
excess: Chiral GC analysis (Chirasil-dex; 80 to 1008C at 58C/
min, then 100 to 1808C at 18C/min, 10 psi head column
pressure; tR(major) ˆ 68.37 min, tR(minor) ˆ 68.74 min).
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5b): yield: 84%
1
(228 mg, 0.87 mmol). H NMR (CDCl3): d ˆ 1.17 (t, 3H, J ˆ
7.1 Hz), 1.82 (m, 2H), 2.15 (m, 2H), 2.60 (br d, 1H, J ˆ 5.8 Hz),
2.64 (m, 1H), 2.81 (m, 1H), 3.47 (m, 2H), 3.89 (dq, 1H, J ˆ 9.5,
7.1 Hz), 4.08 (m, 1H), 4.66 (dd, 1H, J ˆ 5.4, 6.0 Hz), 5.54 (m,
1H), 5.74 (m, 1H), 7.14 (m, 5H); 13C NMR (CDCl3): d ˆ 15.2
(CH3), 31.0 (CH2), 32.0 (CH2), 35.0 (CH2), 64.4 (CH2), 72.6
(CH), 77.3 (CH), 98.5 (CH), 124.9 (CH), 125.8 (CH), 126.5
(CH), 128.4 (CH), 128.5 (CH), 142.2 (C); HRMS (EI):
1
(221 mg, 0.84 mmol). H NMR (CDCl3): d ˆ 1.28 (t, 3H, J ˆ
7.1 Hz), 2.29 (m, 2H), 3.40 (br s, 1H), 3.64 (dq, 1H, J ˆ 9.5,
7.0 Hz), 3.84 (s, 3H), 4.06 (dq, 1H, J ˆ 9.5, 7.0 Hz), 4.38 (m, 1H),
4.63 (d, 1H, J ˆ 7.8 Hz), 4.83 (t, 1H, J ˆ 5.4 Hz), 5.39 (m, 1H),
5.82 (m, 1H), 6.96 (d, 2H, J ˆ 8.7 Hz), 7.35 (d, 2H, J ˆ 8.7 Hz);
13C NMR (CDCl3): d ˆ 15.2 (CH3), 31.1 (CH2), 64.5 (CH2), 76.5
(CH), 78.9 (CH), 98.6 (CH), 113.8 (CH3), 124.8 (CH), 125.5
‡
À
[M HOC2H5] , calcd. for C14H16O2: 216.1150; found: 216.115.
[a]D25: ‡ 70.7 (c 1.00, CHCl3). Assay of enantiomeric excess:
Chiral GC analysis (Chirasil-dex; 80 to 1008C at 58C/min, then
100 to 1808C at 18C/min, 15 psi head column pressure;
tR(major) ˆ 82.16 min, tR(minor) ˆ 81.35 min).
‡.
(CH), 128.6 (CH), 132.0 (C), 159.4 (C); HRMS (EI): [M] ,
calcd. for C15H20O4: 264.1362; found: 264.136. [a]D25: ‡ 76.4 (c
1.02, CHCl3). Assay of enantiomeric excess: Chiral GC analysis
(Chirasil-dex; 80 to 1008C at 58C/min, then 100 to 1808C at
18C/min, 10 psi head column pressure; tR(major) ˆ 75.00 min,
tR(minor) ˆ 74.31 min).
(2S,6R,7S,8R)-3,6-Dihydro-2H-pyran (5g): mp 1398C;
1
yield: 78% (391 mg, 0.78 mmol). H NMR (CDCl3): d ˆ 1.02
(s, 9H), 1.18 (t, 3H, J ˆ 7.1 Hz), 2.19 (m, 2H), 2.47 (d, 1H, J ˆ
7.9 Hz), 3.30 (dq, 1H, J ˆ 9.5, 7.1 Hz), 3.72 (dq, 1H, J ˆ 9.5,
7.1 Hz), 3.78 (td, 1H, J ˆ 7.8, 2.6 Hz), 4.63 (dd, 1H, J ˆ 6.1,
4.6 Hz), 4.73 (m, 1H), 4.82 (d, 1H, J ˆ 7.6 Hz), 5.63 (m, 1H),
5.80 (m, 1H), 7.40 (m, 13H), 7.68 (dd, 2H, J ˆ 7.8, 1.4 Hz);
13C NMR (CDCl3): d ˆ 15.5 (CH3), 19.8 (C), 27.4 (CH3), 31.2
(CH2), 64.6 (CH2), 73.5 (CH), 76.3 (CH), 77.3 (CH), 98.4 (CH),
124.9 (CH), 127.9 (CH), 127.6 (CH), 127.8 (CH), 128.2 (CH),
128.4 (CH), 129.8 (CH), 129.9 (CH), 136.4 (CH), 136.5 (CH),
133.7 (C), 134.4 (C), 141.7 (C). [a]D25: ‡ 39.3 (c 1.04, CHCl3.
(2S,6R,7R)-3,6-Dihydro-2H-pyran (5c): yield: 77%
1
(207 mg, 0.77 mmol). H NMR (CDCl3): d ˆ 1.26 (t, 3H, J ˆ
7.1 Hz), 2.26 (m, 2H), 3.30 (br s, 1H), 3.58 (dq, 1H, J ˆ 9.6,
7.1 Hz), 3.98 (dq, 1H, J ˆ 9.6, 7.1 Hz), 4.32 (m, 1H), 4.61 (d, 1H,
J ˆ 7.0 Hz), 4.79 (t, 1H, J ˆ 5.5 Hz), 5.38 (m, 1H), 5.84 (m, 1H),
7.33 (m, 4H); 13C NMR (CDCl3): d ˆ 15.2 (CH3), 30.9 (CH2),
64.5 (CH2), 76.0 (CH), 78.4 (CH), 98.4 (CH), 125.1 (CH), 125.2
1218
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1215 1219

Synthesis of 2,6-Disubstituted 2H-Dihydropyrans
COMMUNICATIONS
‡
À
HRMS (EI): [M HOC2H5 t-Bu] , calcd. for C25H23O3Si:
399.1417; found: 399.141.
Vaultier, B. Plunian, L. Toupet, Heterocycles 1999, 50,
703 711; d) G. Lorvelec, M. Vaultier, Tetrahedron Lett.
1998, 39, 5185 5188; e) B. B. Toure, H. R. Hoveyda, J.
Tailor, A. Ulaczyk Lesanko, D. G. Hall, Chem. Eur. J.
2003, 9, 466 474 and references cited therein.
Acknowledgements
[8] For synthesis of 1, see: C. Rasset-Deloge, P. Martinez-
Fresneda, M. Vaultier, Bull. Soc. Chim. Fr. 1992, 129,
285 290 and ref.[7e]
[9] M. Deligny, F. Carreaux, B. Carboni, L. Toupet, G.
Dujardin, Chem. Commun. 2003, 276 277.
We are grateful to MJENTfor a grant. We thank Prof. E. N.
Jacobsen and D. Chavez (Harvard University, Cambridge,
USA) for a gift of (1R,2S)-2 and Paul Le Maux (UMR 6509,
Rennes France) for his help in chiral GC analysis.
[10] K. Gademan, D. E.; Chavez, E. N. Jacobsen, Angew.
Chem. Int. Ed. 2002, 41, 3059 3061.
References and Notes
[11] During the preparation of our manuscript, very similar
results were reported by Hall and Gao: X. Gao, D. G.,
Hall, J. Am. Chem. Soc. 2003, 125, 9308 9309.
[1] Comprehensive Asymmetric Catalysis, Vols. 1 3, (Eds.:
E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer:
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[2] D. S. Matteson, Stereodirected Synthesis with Organo-
boranes; Springer: Berlin, 1995.
[3] For selected recent references related to alkenyl- and
dienylboronic esters, see: a) G. C. Micalizio, S. L.
Schreiber, Angew. Chem. Int. Ed. 2002, 41, 3272 3276;
b) G. W. Kabalka, G. Dong, B. Venkataiah, Org. Lett.
2003, 5, 893 895; c) E. Tyrrell, P. Brookes, Synthesis
2003, 469 483; d) C. J. Chapman, C. G. Frost, Adv.
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Jamison, Angew. Chem. Int. Ed. 2003, 42, 1364 1367;
f) X. Gao, D. G. Hall, Tetrahedron Lett. 2003, 44, 2231
2235; g) J. Uenishi, K. Matsui, A. Wada, Tetrahedron
Lett. 2003, 44, 3093 3096.
[4] A. Suzuki, H. C. Brown, Organic Syntheses via Boranes,
Aldrich Chemical Company, Milwaukee, USA, 2003,
Vol. 3.
[5] For cyclopropanations of optically active boronates, see:
a) I. E. Marko, T. Kumamoto, T. Giard, Adv. Synth.
Catal. 2002, 344, 1063 1067; b) J. E. A Luithle, J.
Pietruszka, Eur. J. Org. Chem. 2000, 2557 2562; c) Pie-
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4293 4300 and references cited therein.
[6] For 1,3-cycloadditions of optically active boronates and
boratranes, see: a) B. Jiang, A. Zhang, Y. Kan, Chin. J.
Chem. 1999, 17, 293 299; b) C. D. Davies, S. P. Marsden,
E. S. E. Stokes, Tetrahedron Lett. 2000, 41, 4229 4233;
c) C. D. Davies, S. P. Marsden, E. S. E. Stokes, Tetrahe-
dron Lett. 1998, 39, 8513 8516 and references cited
therein.
1
[12] The 400 MHz H NMR spectra were significantly differ-
ent for the two diastereomers of Mosher×s esters
prepared from racemic 4. 96% ee determined by
19F NMR was confirmed by the chiral GC result, no
racemisation occurred during the derivatisation. The
determination of the absolute configuration, established
according to the literature: J. A. Dale, D. L. Dull, H. S.
Mosher, J. Org. Chem. 1969, 34, 2543 2549; was based
on the difference of chemical shifts of the O-CH2-CH3
(d ˆ 1.09 (4R) and 1.12 ppm (4S)).
[13] M. Vaultier, F. Truchet, B. Carboni, R. W. Hoffmann, I.
Denne, Tetrahedron Lett. 1987, 28, 4169 4172; J. Y.
Lallemand, Y. Six, L. Ricard, Eur. J. Org. Chem. 2002,
503 513 and references cited therein.
[14] Crystal data for 5 g: C31H76Si2O8, Mrˆ 502.71, triclinic,
P-1, a ˆ 9.3044(2), b ˆ 9.9061(2), c ˆ 16.2873(5) ä, a ˆ
73.005(1)8, b ˆ 82.729(1)8, g ˆ 89.475(2)8, Vˆ 1423.49(6)
3
3
ä , Z ˆ 2, Dx ˆ 1.173 Mg ¥ m , l(MoKa) ˆ 0.71073 ä,
1
m ˆ 1.15 cm , F(000) ˆ 540, Tˆ 293 K. The absolute
configuration is unambiguously confirmed (Flack pa-
rameterˆÀ 0.02(9)). The two molecules of the asym-
metric unit are independent and have the same absolute
configuration. Crystallographic data (excluding structure
factors) have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publica-
tion no. CCDC 218262. Copies of the data can be
obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [Fax: int. code
( ‡ 44)-1223-336-033; E-mail: deposit@ccdc.cam.ac.uk].
[15] Results reported by Hall and Gao showed that a one-pot
transformation is possible provided that less catalyst
(0.5%) and molecular sieves were used.
[7] For Diels Alder reactions of optically active boronates,
see: a) P. Y. Renard, J. Y. Lallemand, Tetrahedron Asym-
metry 1996, 7, 2523 2524; b) A. Zhang, Y. Kan; B. Jiang,
Tetrahedron 2001, 57, 2305 2309; c) J. Mortier, M.
[16] Y. Kobayashi, Y. Takemoto, T. Kamijo, H. Harada, Y.
Ito, S. Terashima, Tetrahedron. 1992, 48, 1853 1868.
Adv. Synth. Catal. 2003, 345, 1215 1219
asc.wiley-vch.de
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